The blood-vascular interface is the non-thrombogenic surface of the intimal endothelium that, at predilected sites, has been shown to be more susceptible to the influence of such naturally-occuring hemodynamic factors as oscillatory blood flow, shear and tensile wall stress, and blood pressure. Electron microscopic and histochemical observations of vascular disease processes such as atherosclerosis and thrombosis have reported alterations in the endothelial cell surface carbohydrate complex prior to or concomitant with these local disturbances at the vessel wall. Based upon this premise, endothelium over the mitral and aortic valves of the heart could serve as an effective model for in vivo studies of macromolecular surface properties in that each of their cusps provides a population of cells typically exposed to two rather different fluid-mechanical events. Therefore, this investigation is intended to characterize and compare the surface topography of the two endothelial surfaces lining each of the cups of these valves and their response to a diet-induced state of hypercholesterolemia by employing cationized ferritin, ruthenium red, peroxidase-, ferritin-, hemocyanin-and microsphere- conjugated lectins (Con A, RCA 120, SBA, WGA, LPA) and glycosidic enzymes in concert with transmission and scanning electron microsocpy. Since these valves are two non-arterial sites considered to be predisposed to endothelial injury, the long-term objective of this study is to develop surface macromolecular profiles for such conditions as hypercholesterolemia, hypertension, and diabetes in an attempt to understand better the structural responses at the vascular wall that precede alterations in endothelial integrity and the subjacent intimal reaction.